Biological Markers

Caloric restriction (CR), undernutrition without malnutrition, remains the only experimental paradigm that has been shown consistently to extend lifespan and slow aging in short-lived species. Decades of research, mostly in laboratory rodents, have shown that CR consistently extends lifespan, reduces or delays the onset of many age-related diseases and slows aging in many physiological systems. In recent years gerontologists interested in CR have focused on two unanswered questions. 1) What is the relevance of this nutritional paradigm to human aging?

Biogerontology is the study of the aging of biological systems. This review addresses the relationship between chemistry and biology during aging, proposing that chemistry is responsible for the aging of biological systems. In the continuing struggle between chemistry and biology, chemistry is always the short-term, tactical winner--death of the individual is inevitable. However, barring the extinction of species, biology is the long-term, strategic victor--life survives, and the struggle continues.

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.

PURPOSE OF REVIEW: The focus of this review is on current research involving long-term calorie restriction and the resulting changes observed in possible biomarkers of aging. Special emphasis will be given to the basic and clinical science studies which are currently investigating the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age and obesity in humans.

A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart.

BACKGROUND: We review studies showing that CR acts rapidly, even in late adulthood, to extend health- and lifespan in mice. These rapid physiological effects are closely linked to patterns of gene expression in liver and heart. Non-human primate and human studies suggest that the signal transduction pathways responsible for the lifespan and health effects of caloric restriction (CR) may also be involved in human longevity. Thus, pharmaceuticals capable of mimicking the effects of CR (and other methods of lifespan extension) may have application to human health.

In previous investigations an impact of cellular copper homeostasis on ageing of the ascomycete Podospora anserina has been demonstrated. Here we provide new data indicating that mitochondria play a major role in this process. Determination of copper in the cytosolic fraction using total reflection X-ray fluorescence spectroscopy analysis and eGfp reporter gene studies indicate an age-related increase of cytosolic copper levels. We show that components of the mitochondrial matrix (i.e. eGFP targeted to mitochondria) become released from the organelle during ageing.

Menopause is the final step in the process referred to as ovarian ageing. The age related decrease in follicle numbers dictates the onset of cycle irregularity and the final cessation of menses. The parallel decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility. Endocrine changes mainly relate to the decline in the negative feedback from ovarian factors at the hypothalamo-pituitary unit.

The concept of biomarkers of aging and age-related disease dates to the early 1980s as scientists engaged in aging research worked to clearly define aging and separate processes from disease with better prediction of both as an objective. The concept of basic aging processes, separate from disease, was then, and still is, not universally accepted. While the search for biomarkers of aging has a relatively long and difficult history, the search for biomarkers of disease is conceptually more straightforward.

Cataract formation represents a serious problem in the elderly and has a large impact on healthcare budget. Aging and cataract formation are relatively complex phenomena, both in vivo and in vitro. Telomeres are special structures at the end of chromosomes. They shorten during each round of replication, and this has been characterized as a mitotic counting mechanism.